Excess fibroblast growth factor 23 in alcoholic osteomalacia is derived from the bone

This is the authors' abstract. We don't add key points for this paper.

Excess fibroblast growth factor 23 (FGF23), a mature osteocyte-derived phosphaturic hormone, causes chronic hypophosphatemic osteomalacia in adults. This rare condition was recently reported in 2 alcoholic patients, with marked improvement upon cessation of alcohol consumption, suggesting a link between alcohol and FGF23-related hypophosphatemia within the highly limited cases. This study aimed to investigate whether the source of excess FGF23 in alcohol-induced FGF23-related hypophosphatemic osteomalacia is the bone or the other organs. To achieve this goal, an immunohistochemical approach for the bone obtained from a patient was employed. Initial attempts at quantifying FGF23 in the bone using conventional immunohistochemistry (IHC) faced issues in quantifiability and sensitivity for low FGF23 expression levels. Therefore, next-generation IHC with phosphor-integrated dots (PIDs) was applied, which enabled the quantification of FGF23 expression in the bone across a broad range. Preliminary analyses using IHC with PIDs on normal bone samples (n = 12) provided a reference level (154.5 PID particles per cell). IHC with PIDs quantified suppressed physiological FGF23 expression in the bone samples from 3 patients with tumor-induced osteomalacia, where FGF23 is oversecreted from a tumor (13.6 PID particles per cell). Subsequently, bone samples obtained from a 70-yr-old male with alcohol-induced FGF23-related hypophosphatemic osteomalacia were analyzed, showing a higher number of PID particles per cell (199.4 PID particles per cell) than the reference level. This study suggests that orthotopic, bone-derived FGF23 is implicated in alcohol-induced FGF23-related hypophosphatemic osteomalacia. Furthermore, the study also demonstrated that highly sensitive IHC with PIDs could aid in the differential diagnosis of FGF23-related hypophosphatemia of unknown origin. Specifically, a bone sample with a low number of PID particles per cell indicates an excess ectopic secretion of FGF23; a bone sample with a normal to high number of PID particles per cell indicates an excess orthotopic secretion of FGF23.